11-Chlor-5,6-dihydro-6-oxomorphanthridin | 723-86-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯氮卓类
• 英文名称: 11-Chlor-5,6-dihydro-6-oxomorphanthridin
• 英文别名: 11-Chloro-5,11-dihydro-dibenzo[b,e]azepin-6-one；11-chloro-5,11-dihydrobenzo[c][1]benzazepin-6-one
• CAS: 723-86-4
• 化学式: C₁₄H₁₀ClNO
• 分子量: 243.692
• InChiKey: YVGYCHJINBDOEE-UHFFFAOYSA-N

物化性质

• 熔点：
  226 °C (decomp)
• 沸点：
  299.1±39.0 °C(Predicted)
• 密度：
  1.35±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  17
• 可旋转键数：
  0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  29.1
• 氢给体数：
  1
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  11-Chlor-5,6-dihydro-6-oxomorphanthridin 在 氨 、 氢气 、 镍 作用下， 以 乙醇 、 乙腈 为溶剂， 60.0~80.0 ℃ 、6.08 MPa 条件下， 反应 6.5h， 生成 (6-oxo-5,11-dihydro-6H-dibenzazepin-11-yl)methylamine
  参考文献：
  名称：

  New triazine derivatives as potent modulators of multidrug resistance

  摘要：

  A series of 70 triazine derivatives have been synthesized and tested for their capacity to modulate multidrug resistance (MDR) in DC-3F/AD and KB-A1 tumor cells in vitro, in comparison with verapamil (VRP), a calcium channel antagonist currently used in therapy as an antihypertensive drug, which also shows MDR modulating activity. Among the 12 selected compounds, 16 (S9788) showed high MDR reversing properties in vitro (300- and 6-fold VRP at 5-mu-M in DC-3F/AD and KB-A1 cells, respectively) and induced a strong accumulation of adriamycin. The relationship between the increase of ADR accumulation and the fold reversal induced by these compounds and their lack of effects on the sensitive DC-3F cells suggest that they act mainly by inhibiting the P-glycoprotein (Pgp) catalyzed efflux of cytotoxic agents, as already described for a majority of MDR modulators. In vivo, in association with the antitumor drug vincristine (0.25 mg/kg), 16 (100 mg/kg) increased the TIC by 39% in mice bearing the resistant tumor cell line P388/VCR. According to these interesting properties, 16 was selected for a clinical development because it was more bioavailable than 34, even though it was less active.

  DOI：

  10.1021/jm00091a017
• 作为产物：
  描述：

  蒽醌 在 sodium tetrahydroborate 、 氯化亚砜 、 sodium azide 、 硫酸 作用下， 以 甲醇 、 氯仿 为溶剂， 反应 19.0h， 生成 11-Chlor-5,6-dihydro-6-oxomorphanthridin
  参考文献：
  名称：

  选择性小分子神经肽Y Y2受体拮抗剂的合成及合成孔径雷达

  摘要：

  报告了高效和选择性的小分子神经肽 Y Y2 受体拮抗剂。从 HTS 鉴定的命中分子N- (4-ethoxyphenyl)-4-[hydroxy(diphenyl)methyl]piperidine-1-carbothioamide的系统 SAR 探索导致发现了高效的 NPY Y2 拮抗剂16 (CYM 9484)和54 (CYM 9552)，IC 50值分别为 19 nM 和 12 nM。

  DOI：

  10.1016/j.bmcl.2012.04.107

文献信息

• Application of the Guanidine-Acylguanidine Bioisosteric Approach to Argininamide-Type NPY Y2 Receptor Antagonists
  作者：Nikola Pluym、Albert Brennauer、Max Keller、Ralf Ziemek、Nathalie Pop、Günther Bernhardt、Armin Buschauer

  DOI：10.1002/cmdc.201100241

  日期：2011.9.5

  structural elements, but they compromise the drug‐likeness of numerous biologically active compounds, including ligands of G‐protein‐coupled receptors (GPCRs). As part of a project focused on the search for guanidine bioisosteres, argininamide‐type neuropeptide Y (NPY) Y2 receptor (Y2R) antagonists related to BIIE0246 were synthesized. Starting from ornithine derivatives, NG‐acylated argininamides were obtained

  诸如胍基等强碱性基团是至关重要的结构元素，但它们会损害许多生物活性化合物的药物样，包括G蛋白偶联受体（GPCR）的配体。作为致力于寻找胍类生物等位基因的项目的一部分，合成了与BIIE0246相关的精氨酸酰胺型神经肽Y（NPY）Y 2受体（Y 2 R）拮抗剂。从鸟氨酸衍生物开始，N ģ -acylated argininamides通过胍基化量身定做的单-Boc保护的得到Ñ -acyl-小号-methylisothioureas。研究了这些化合物的Y 2 R拮抗作用（钙测定），Y 2R亲和力和NPY受体亚型选择性（流式细胞术结合测定）。大多数N G取代的（S）-精氨酰胺显示出与母体化合物相似的Y 2 R拮抗活性和结合亲和力，而带有末端胺的N G酰化或氨基甲酰化类似物则更为出色（Y 2 R：K i和K B值在低纳摩尔范围内）。这表明化合物的碱性虽然比胍的碱度低4-5个数量级，但足以与Y 2的酸性氨基酸形成关键相互作用R
• [EN] NON-PEPTIDIC NEUROPEPTIDE Y RECEPTOR MODULATORS<br/>[FR] MODULATEURS DE RÉCEPTEUR DE NEUROPEPTIDE Y NON PEPTIDIQUE
  申请人：ROBERTS EDWARD

  公开号：WO2014116684A1

  公开（公告）日：2014-07-31

  The invention provides compounds that are modulators of neuropeptide Y (NPY) receptors, which can be selective inhibitors of NPY receptor Y2R. NPY receptor modulatory compounds are of the general formula Ar2-Y-Ar1-W-Ar3, wherein the variables are as defined herein. Compounds of the invention can be used for treatment of malconditions in patients wherein modulation of an NPY receptor is medically indicated, for example including drug or alcohol abuse, anxiety disorders, depression, stress-related disorders, neurological disorders, nerve degeneration, osteoporosis or bone loss, sleep/wake disorders, cardiovascular diseases, obesity, anorexia, inovulation, fertility disorders, angiogenesis, cell proliferation, learning and memory disorders, migraine and pain.

  该发明提供了调节神经肽Y（NPY）受体的化合物，这些化合物可以是NPY受体Y2R的选择性抑制剂。NPY受体调节化合物的一般结构式为Ar2-Y-Ar1-W-Ar3，其中变量如本文所定义。该发明的化合物可用于治疗患者的异常情况，其中调节NPY受体在医学上指示，例如包括药物或酒精滥用、焦虑症、抑郁症、与压力相关的疾病、神经系统疾病、神经退化、骨质疏松或骨质流失、睡眠/清醒障碍、心血管疾病、肥胖、厌食症、排卵障碍、生育障碍、血管生成、细胞增殖、学习和记忆障碍、偏头痛和疼痛。
• Isoindolin-1-one derivative and antiarrhythmic agent
  申请人：Kyowa Hakko Kogyo Co., Ltd.

  公开号：US04849441A1

  公开（公告）日：1989-07-18

  Isoindolin-1-one compounds represented by the following formula (I); ##STR1## wherein n represents an integer of 1 to 6; m represents 0 or 1; R.sub.1, R.sub.2 and R.sub.3 are each independently hydrogen or lower alkyl, and when m is 1, R.sub.1 and one of R.sub.2 and R.sub.3 may form a five-membered or six-membered ring over N atom; X represents hydrogen or hydroxy; Ar represents naphthyl, pyridyl or substituted phenyl represented by the formula (II); Ar and X may form a lactone ring; ##STR2## [wherein Y represents carboxyl, lower alkoxycarbonyl, carbamoyl, N,N-lower alkyl-substituted carbamoyl or amino represented by the formula (III): ##STR3## (wherein R.sub.6 and R.sub.7 are each independently hydrogen, lower alkyl or lower alkanoyl); R.sub.4 and R.sub.5 are each independently hydrogen, lower alkyl, cyano or halogen]} or a pharmaceutically acceptable acid addition salt or metal salt thereof have an excellent antiarrhythmic activity.

  以以下公式（I）表示的Isoindolin-1-one化合物；其中n表示1到6的整数；m表示0或1；R.sub.1，R.sub.2和R.sub.3分别独立地表示氢或较低的烷基，当m为1时，R.sub.1和R.sub.2和R.sub.3中的一个可以形成以N原子为中心的五元环或六元环；X表示氢或羟基；Ar表示naphthyl，pyridyl或由以下公式（II）表示的取代苯基；Ar和X可以形成内酯环；其中Y表示羧基，较低的烷氧羰基，氨基或由以下公式（III）表示的N，N-较低烷基取代的氨基：（其中R.sub.6和R.sub.7分别独立地表示氢，较低烷基或较低烷酰基）；R.sub.4和R.sub.5分别独立地表示氢，较低烷基，氰基或卤原子；或其药学上可接受的酸盐或金属盐具有优异的抗心律失常活性。
• Alkoxy-11 dibenzo[b,e]azépinones-6 à activité anti-convulsivante
  作者：V Pestellini

  DOI：10.1016/0223-5234(88)90145-6

  日期：1988.10
• OKAZAKI, KEI;OSHIMA, ETSUO;OBASE, HIROYUKI;OIJI, YOSHIMAZZ;NITO, MASAAKI;+
  作者：OKAZAKI, KEI、OSHIMA, ETSUO、OBASE, HIROYUKI、OIJI, YOSHIMAZZ、NITO, MASAAKI、+

  DOI：——

  日期：——